Dry eye disease (DED) is a common disease that can impair quality of life significantly. Its prevalence increases with advancing age, and the economic burden of the disease on both a patient and the society is increasing with elongation of life expectancy. The diagnosis and treatment of DED are often difficult due to the discordance between symptoms and signs of the disease. Recent studies have suggested the role of neurological or psychological factors in the development of dry eye symptoms and discrepancy of the symptoms and signs, particularly in elderly patients. In this review, the authors discuss the association of DED with various psychiatric and neurological disorders. In addition to psychiatric conditions, including depression, anxiety, stress, posttraumatic stress disorder and sleep disorders, medications for the psychiatric disorders have association with DED. Neurological disorders, such as neuropathic pain, chronic pain syndrome, peripheral neuropathy and several central nervous system disorders, are related to DED. Treatment of DED, combined with psychiatric or neurological disorders, is also discussed. Attention should be paid to the DED patients with discordant symptoms and signs, and unsatisfactory response to conventional treatment for associated psychiatric or neurological disorders, as well as an integrated treatment approach, could be helpful for these patients.